Multiple sclerosis (MS) is an autoimmune demyelinating disease and a common cause of neurological disability in young adults. The modest heritability of MS reflects complex genetic effects and multifaceted gene-environment interactions. The human leukocyte antigen (HLA) region is the strongest susceptibility locus for MS, but a genome-wide association study recently identified new susceptibility genes. Progress in high-throughput genotyping and sequencing technologies and a better understanding of the structural organization of the human genome, together with powerful brain-imaging techniques that refine the phenotype, suggest that the tools could finally exist to identify the full set of genes influencing the pathogenesis of MS.